Pro-opio melanocortin is the precursor to a number of important nueroactive peptides, including ACTH, a, b-, and g-melanocyte hormones, b-endorphin and N-terminal fragment that potentiates the steriodogenic action of ACTH. The objective of this research is to elucidate the mechanisms of expression of pro-opiomelanocortin and related genes in pituitary and extrapituitary tissues. We wish to define the intracellular sites of action of various positive and negative regulator molecules of POMC production (such as corticotropin releasing factor(s), glucocorticoids, and neurotransmitters). To perform this study it is necessary to have a detailed knowledge of the number and structure of POMC genes. By generating specific nucleic acid probes from POMC genomic clones, the study of POMC gene expression will be possible at the levels of transcription, nuclear mRNA processing, transport of mRNA from nucleus to cytoplasm, mRNA stability and translational control. Because of the importance of POMC peptides such as b-endorphin and a-MSH in complex behavioral responses, the expression of POMC in extrapituitary tissues such as the hypothalamus and amygdala will be of particular interest to us. Therefore, with the POMC system, we can ask how a gene or a family of closely related genes can be differentially expressed in different tissues. In the longer range view, the elucidation of expression of POMC genes may help to explain how the production of other neuroactive peptides can be co-ordinated to produce complex behavioral responses.